Wnt5a as a Predictor in Poor Clinical Outcome of Patients and a Mediator in Chemoresistance of Ovarian Cancer
Wnt5a as a Predictor in Poor Clinical Outcome of Patients and a Mediator in Chemoresistance of Ovarian Cancer
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Wnt5a 作为患者不良临床结果的预测因子和卵巢癌化疗耐药的调节因子
DOI：
10.1097/igc.0b013e31820aaadb
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发表时间：
2011-02-01
影响因子：
4.8
通讯作者：
Zheng, Jianhua
中科院分区：
文献类型：
--
作者：
Peng, Chunjie;Zhang, Xiaolei;Zheng, Jianhua
简介：Wnt 5a调节多种信号通路，控制广泛的细胞过程，包括细胞增殖、分化和凋亡。然而，目前还不清楚Wnt 5a是否参与介导癌症的化疗耐药性。方法：采用免疫组化方法检测Wnt 5a在卵巢癌、良性肿瘤和正常卵巢组织中的表达，并分析其与卵巢癌临床病理参数和生存期的关系。建立了两种稳定的细胞系，即SKOV 3/Wnt 5a，其过表达Wnt 5a，和SKOV 3/miRNA，其使用microRNA（miRNA）下调Wnt 5a表达。Wnt 5a表达水平通过半定量逆转录-聚合酶链反应、Western印迹分析和免疫荧光测定进行评价。结果：Wnt 5a在卵巢癌组织中的表达水平明显高于良性肿瘤和正常卵巢组织。高水平的Wnt 5a表达与国际妇产科联合会的分期相关，与低水平的Wnt 5a表达相比，高水平的Wnt 5a表达显著预测了较差的总生存期和无进展生存期。此外，与正常和空载体对照组相比，Wnt 5a过表达的SKOV 3/Wnt 5a细胞对化疗药物的敏感性降低（P < 0.05）。结论：Wnt 5a免疫阳性表达可能是卵巢癌患者预后的一个有用指标。这些结果首次阐明了Wnt 5a在调节卵巢癌细胞对抗癌药物的化疗敏感性方面发挥重要作用的可能性。
Introduction: Wnt5a regulates numerous signaling pathways controlling a wide range of cellular processes, including cell proliferation, differentiation, and apoptosis. However, it is still unclear whether Wnt5a is involved in mediating chemoresistance in cancer. We studied the correlation of Wnt5a expression with clinicopathologic parameters and survival in epithelial ovarian cancer and the effect of Wnt5a expression on chemoresistance of ovarian cancer cells.Methods: Wnt5a expression was immunohistochemically examined in ovarian cancer, benign tumor, and normal ovarian tissues. Two stable cell lines were established, namely, SKOV3/Wnt5a, which overexpressed Wnt5a, and SKOV3/miRNA, which downregulated Wnt5a expression using microRNA (miRNA). Wnt5a expression level was evaluated by semiquantitative reverse transcription-polymerase chain reaction, Western blot analysis, and immunofluorescence assay. The sensitivity of all transfected and untransfected cell lines to chemotherapeutic drugs (paclitaxel, oxaliplatin, 5-fluorouracil, epirubicin, and etoposide) was detected by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assay.Results: Wnt5a was found to be significantly higher in ovarian cancer compared with benign tumors and normal ovaries. High levels of Wnt5a expression were associated with the International Federation of Gynecology and Obstetrics stage and significantly predicted a poorer overall survival and progression-free survival compared with low Wnt5a expression. In addition, Wnt5a overexpression in SKOV3/Wnt5a cells decreased chemosensitivity compared with normal and empty vector controls (P < 0.05). Alternatively, Wnt5a down-regulation in SKOV3/miRNA cells led to a significant increase in chemosensitivity (P < 0.05).Conclusions: Wnt5a immunoreactivity may be a useful prognostic indicator in patients with ovarian cancer. These results clarified for the first time the possibility that Wnt5a plays an important role in regulating chemosensitivity to anticancer drugs in ovarian cancer cells.